1. Field of the Invention
The present disclosure relates to a radioactive labeled compound with a tetrahydropyridothieno[2,3-d]pyrimidine skeleton that can in one aspect provide information for detecting a secondary mutation of an epidermal growth factor receptor (EGFR).
2. Description of Related Art
Lung cancer, which is the number one worldwide cause of death due to cancer, is roughly divided into small cell lung cancer and non-small cell lung cancer according to the histological type thereof. It is known that the EGFR gene that codes for EGFR, which is a transmembrane tyrosine kinase receptor, has mutated in 10% to 30% of patients with non-small cell lung cancer which accounts for 80% of lung cancer. The EGFR is activated when mutated and this activation is considered to play a role in cancer growth, etc. Furthermore, once the mutation of the EGFR gene was found, an EGFR-TKI (an epidermal growth factor receptor tyrosine kinase inhibitor), which is a molecular target drug, was considered to be more effective than common anticancer agents. In recent years, therefore, when a patient is diagnosed as having lung cancer, the possible presence of a mutation in the genes of the patient is checked by a genetic test (for example, Hsin Hsien Yeh et al., PNAS, Jan. 25, 2011; vol. 108, no. 4, 1603-1608). These genetic tests are often carried out using cancer tissue collected by biopsy. However, an invasive biopsy on a cancer patient has various risks associated with it and also results in a heavy physical burden. Therefore, there has been a need for new methods that provide alternatives to conventional genetic tests and that avoid various risks associated with the biopsy. As one of the methods, radioactive imaging probes for nuclear medicine diagnosis that can detect EGFR in cancer have been studied (for example, M. A. Pantaleo et al., Annals of Oncology 2009, 20: 213-226; and Emily B. Corcoran et al., Medicinal Research Reviews 2014, 34: 596-643).
Despite the success of the EGFR-TKI, resistance develops within a year and as a result, the EGFR-TKI may no longer provide sufficient therapeutic effects. Since a secondary mutation is considered to play a role in approximately half the cases that develop resistance, it becomes necessary to conduct the genetic test again after the start of treatment with the EGFR-TKI.